Project Summary BACKGROUND The Hepatitis B Research Network (HBRN) was created in 2008 to address several research challenges regarding chronic hepatitis B (CHB). The HBRN was charged with establishing a large cohort of patients with hepatitis B virus (HBV) infection to study the natural history of HBV infection and designing treatment protocols(s) to compare monotherapy to combination therapy using clinical outcomes as endpoints. There are 12 consortia (22 clinical sites) recruiting adult and pediatric patients including the Toronto site (University Health Network, Toronto General Hospital & Hospital for Sick Children) to address the following specific aims: Specific Aims: 1. To describe participants with hepatitis B virus (HBV) infection in a prospective cohort in the United States (US) and Canada and identify predictors of disease activation and progression 2. To define the role of limited duration peginterferon alfa-2a in the presence of tenofovir for treating people with chronic hepatitis B (Immune Active (IA) Trial) 3. To evaluate ?off treatment? safety and sustained responses after treatment with entecavir and peginterferon alfa-2a in the treatment of chronic hepatitis B in HBeAg positive adults who are in the immune tolerant phase. (Immune Tolerant (IT) Trial) 4. The clinical and virological status of chronic HBV infection is defined by distinct patterns of immune effector and regulatory responses. 5. To examine if therapeutic HBV suppression will enhance antiviral immune effector responses and reduce immune inhibitory factors in participants with chronic hepatitis B With the highest number of enrolled patients and among the best retention rates in all categories of HBRN studies, Toronto is the leading site among the HBRN consortium. As of October 31st 2016, Toronto clinics have enrolled 437 patients including 300 adult and 137 pediatrics patients in the cohort study from a total number of 2427 (18%) enrolled patients across the network. Toronto also is the leading enrolling site in the two main treatment trials of the HBRN, the Adult Immune Active (IA) study and the pediatric/adult Immune Tolerant (IT) study. Toronto investigators are actively involved in numerous ancillary studies, including the ongoing immunology studies as well as studies on virological and clinical outcomes. Toronto investigators also participate actively on numerous committees throughout the network. Overall, in addition to retaining and recruiting patients, Toronto site has played an important role in the HBRN and will continue to be actively involved in all aspects of the network to ensure its continued success.